The goals of this research are twofold: one is to define the mutational specificity, in terms of target DNA sequence, or chemical carcinogens and of metabolites of such carcinogens after activation by the rat liver microsomal system. Major contributions of this work are expected to be: 1) the extension of currently available bacterial tester systems for detecting mutagens; 2) the introduction of data useful in modeling the pathways of carcinogen interaction with mammalian cells. Goal 2: The first goal will be pursued by working from amino acid replacement determinations using histidinol dehydrogenase (HDH) from Salmonella typhimurium. This approach will provide a unique opportunity for achieving the second goal: the amino acid sequence of HDH from both S. typhimurium and from Escherichia coli. Enzyme from both organisms may conveniently be examined together, and progress toward the second goal will materially support efforts toward achievement of the first. Additional benefits would be 1) quantitation of the extent of evolutionary relatedness of the hisD genes of these organisms. 2) Comparison of the primary sequence of each HDH with those of known dehydrogenases.